Amino-alcohols



Patented Aug. 3," 1937 his to .oxybenzylchloride. 165' grams AMINO-ALCOHOLS Max Bockmiihl, Gustav Ehrh'art, Leonhard Stein,

and Julius Hallensleben,

assignors to Winthrop Chemi- Main, Germany,

Frankfort-on-thm cal Company, Inc., New York, N.'Y., a. corporation of New York No Drawing. Application June 28, 1935, Serial No. 28,944. In

Germany July 5, 1934 4 Claims. 01. zoo-128.5)

i v The present invention relates to amino-alcohols, more particularly to amino-alcohols of the following formula:

ClHr CHOH-CH-X wherein X stands for hydrogen or an alkyl radical, Y for a benzyl radical having one .or more etherified or esterifled hydro cyl groups as substituents. i

'llhfise compounds may be produced by reducing the ketones corresponding with the amino-alcos. This process of reduction proceeds accordthe following equation: I

The compounds may also be obtained by introducing into the corresponding amino-alcohols a benzyl radical having as substituents etherified If desired, the reaction products may be allqrlated. The aminoor esterified .hydroxyl groups.

alcohols thus obtained. form colorless crystals which arerather sparingly soluble in water and alcohol. They are distinguished by an excellent antispasmodic action on the bronchial spasms,

the bile-ducts and the intestine which exceeds greatly that of the known l-phenyl-Z-benzylmethylaminopropanol.

The followingexamples serve to illustrate the inventiom-but they are'not intended to limit it thereto: 1 fl 1. A mixture of 85 grams of 3-methyl-6-methof phenylinethylof benzene are bath fdrsome aminopropanol and 1000 cc. heated to boiling in a water hours. The precipitated phenylmethylaminoalcohol. Its melting point and 209"v C.- The yield is almost quantitative. I

propanol hydrochloride is filtered by suction, the benzene solution is neutralized with alcoholic hydrochloric acid and then filtered. The hydrochloride of phenylmethyhnethoxymethylbenzylamlnopropanol obtained is recrystallized fro lies between 207 (3'.v

' boiled which addition of 10 grams The product obtained'has the following formula:

2. 16.5 grams of iphenylmethylaminopropanol and 9.5 grams of b 3,4-dimethoxybenzylchloride are dissolved in 60 cc. of benzene andthe whole is for hours in a re'flux apparatus. The hydrochloride of phenyl-methylaminopropanol tion and subsequently washed withether. The

filtrate obtained is then shaken. with about 150 cc. of hydrochloric acid of whereby the hydrochloride benzylephedrine separates in per' cent strength an almost quantitative yield. After recrystallization from alcohol the compound melts at a. temperature of 213 C. V

to 214 C. and has the following formula:

3 (OH: c m-cnon- H 0H; OCH

3. 19.5 grams of phenylmethylaminopropanol are dissolved in '75 cc. of benzene and the solution is boiled in a reflux apparatus for 6 hours after of 3,4-methylenedihydroxy- The hydrochloride of phenylbenzylchloride.

methylaminopropanol which crystallizes is filtered by suction and subsequently washed with benzene. From the filtrate the methylenedihydroxybenzene-ephedrine hydrochloride is obv tained in an almost quantitative yield by shaking it with dilute hydrochloric. acid- The hydrochlo- .ride is recrystallized from methanol with addi- The melting point lies between I obtained has tion of ether. 183 C. and 185 C. The product the following formula:

. t CH: cine-cliorr-on OH precipitates on cooling is filtered by sucof 3,4-dimethoxyno water.

4. 16.5 grams of phenylmethylaminopropanol, 9.5 grams of 3,4-ethylenedlhydroxybenzylchloride and 4 times their weight of benzene are heated together to boiling for about 5 hours in a reflux apparatus. The phenylmethylaminopropanol hydrochloride which crystallizes on cooling is fil-' om-Qo-cm 5. 24.5 grams of 3-carbethoxy-4-methoxybenzylchloride, 33 grams of phenylmethylaminopropanel and 100 cc. of benzene are'heated together to boiling for 5 hours'in a reflux apparatus. I

The benzene solution is diluted with ether and the hydrochloride of phenylmethylaminopropanol sequently washed with benzene. The filtrate is shaken with a quantity of hydrochloric acid of 10 per cent strength, sumcient to cause the hye drochloride of the condensation product to separate in the form of an oil. The latter is separated and dissolved in acetone. "After a short time the hydrochloride of 3-carbethoxy-4- methoxybenzyl-ephedrlne crystallizes from the acetone solution. The compound melts at 178 C. after recrystallization from alcohol and has the following formula:

on cm dissolved in 40 cc. of alcohol and the solution 50 is mixed with 17.5grams of meta-ethoxybenzylchloride. The whole is heated for a short time and allowed to stand over night. The hydrochloride of phenylmet'hylaminopropanol formed during the reaction is then precipitated by means 55 of ether, filtered with suction and subsequently washed with ether. The ethereal solution is then shaken with about 150 cc. of hydrochloric acid of 10 per cent strength; The aqueous'hydrochloric acid solution is separated and cooled in ice- After a short time the hydrochloride oi; meta-ethoxybenzyl-ephedrine crystallizes which. when recrystallized from acetic ester, melts at a temperature between 168 C. and 170 C. The product has the following formula:

65 I CHI can-enou-c cmoClHl HOE 7. 25.1 grams of phenylmet minopropanol and 20 grams of 8-benzyloxy-4-methoxybenwlwhich separates is filteredwith suction and subchloride are dissolved in 65 cc. of benzene and the solution is boiled for hours in a reflux apparatus. After cooling the benzene solution is diluted with ether and the hydrochloride of phenylmethylaminopropanol which separates is filtered with suction and subsequently washed with benzene. The filtrate obtained is shaken with about 100 cc. of dilute hydrochloric acid, the hydrochloride of the condensation product separating in a crystalline form. After recrystallization from alcohol of 96 per cent strength the hydrochloride of 3-benzyloxy-4-methoxybenzyl-ephed- I rine melts at. 188C. and has the following formula:

CHI

\vm-O-ocm weclaim:

1. Amino-alcohols of the following general formula:

CaHrCH'OH-CH-CHt I OH: CaHr-CHOH-(J 4 CHI OCH! forming colorless crystals, rather dimcultly soluble in water and alcohol and melting at a temperature of 213 C. to 214 C.

3. The amino-alcohol of the following formula:

forming colorless crystals, rather difiicultly sol- *uble in water and alcohol and melting at a temperature between 207 C. and. 209 C.

4. The amino-alcohol of the following formula: 

